Kadmiyum Klorür Toksisitesinin Karaciğer, Böbrek ve Pankreasta Neden Olduğu Hasarı Melatonin Önler mi?

Year 2023, , 2382 - 2392, 01.12.2023

Erhan Şensoy

https://doi.org/10.21597/jist.1280369

Abstract

Yedinci tehlikeli ağır metal olan Kadmiyum, insan sağlığı için temel risk faktörlerinden birisi olarak ifade edilebilir. Besinlerle veya suyla vücuda alınan Kadmiyum, doku ve organlarda birikerek patolojilere yol açar. Düzenleyici görevleri olan Melatonin, aynı zamanda antioksidan bir hormondur. Çalışmanın amacı, oral ve intraperitonal yolla CdCl2 verilen gebe farelerin karaciğer, böbrek ve pankreaslarında belirlenen patolojilerin önlenmesinde melatoninin koruyucu rolünün araştırılmasıdır. Sunulan çalışmada gebelik sürecinde Cd alımı arttığı için gebe fareler kullanıldı. 42 gebe fare ile yedi grup (n:6) oluşturuldu. Kontrol (I.) grubuna oral yolla serum fizyolojik verildi. II. gruba CdCl2, III. gruba Melatoin, IV. gruba CdCl2+Melatoin oral yolla verildi. V. gruba CdCl2, VI. gruba Melatoin, VII. gruba CdCl2+Melatoin intraperitonal yolla verildi. Her iki uygulama yönteminde CdCl2 için 2 mg/kg/bw, Melatonin için 3 mg /kg/bw kullanıldı. Rutin histolojik işlemler gerçekleştirilen karaciğer, böbrek ve pankreas dokuları Hematoksilen-Eozinle boyandı. Işık mikroskobu ve elektron mikroskobu kullanılarak karşılaştırma yapıldı. CdCl2 verilen grupların ortalama organ ağırlıklarında artış belirlenirken, CdCl2+Mel gruplarında ortalama organ ağırlıklarının azaldığı görüldü (p: 0.02). Uygulama gruplarında CdCl2 kaynaklı patolojiler belirlenirken, CdCl2+Mel verilen gruplarda patolojilerin azaldığı belirlendi. İyileşmenin en çok karaciğerde olduğu görüldü. Melatonin’in karaciğer, böbrek ve pankreasta görülen CdCl2 kaynaklı patolojilerin tedavisinde etkili olabileceği belirlendi. Gebelik döneminde kadmiyuma yoğun olarak maruz kalan kadınların, uyku düzenlerine dikkat etmeleri ve melatonin takviyesi almaları önerilir. Kadmiyum maruziyetine karşı melatoninin diğer organlardaki etkisinin belirlenmesi için uzun süreli çalışmalara ihtiyaç olduğu düşünülmektedir.

Keywords

Kadmiyum, Melatonin, Toksisite, Gebelik

Does Melatonin Prevent Damage Caused by Cadmium Chloride Toxicity to the Liver, Kidney, ve Pancreas?

Abstract

Cadmium, the seventh dangerous heavy metal, it may be one of the main risk factors for human health. Cadmium taken into the body with food or water causes pathologies by accumulating in tissues ve organs. Melatonin, which has regulatory functions, is also an antioxidant hormone. The aim of this study is to investigate the protective role of melatonin in the prevention of pathologies determined in the liver, kidney ve pancreas of pregnant mice given CdCl2 via oral ve intraperitonally. Pregnant mice were used because Cd uptake was increased during pregnancy. Seven groups (n:6) were formed with 42 pregnant mice. The saline was given to the control (first) group orally. CdCl2 was given in group II, Melatoin was given Group III, CdCl2+Melatoin was given Group IV orally. CdCl2 was given in group V, Melatoin was given Group VI, CdCl2+Melatoin was given Group VI intraperitoneally. For the both application method 2 mg/kg/bw CdCl2 and 3 mg/kg/bw Melatonin were used. Hematoxylin-Eosin was applied to the tissues for which routine histological procedures were performed. For evaluation used the light and electron microscope. While an increase determined in average organ weights in CdCl2 groups, the average organ weights in CdCl2+Mel groups was decreased. While pathologies were observed in CdCl2 groups, the pathologies decreased in CdCl2+Mel groups. Healing effect of Melatonin was mostly in the liver. Melatonin may be effective to treatment pathologiesons in the liver, kidney and pancreas. Pregnant women exposed to cadmium during should pay attention to their sleep patterns and take melatonin supplements. Long-term studies are needed to determine effect of melatonin in other organs against cadmium exposure.

Keywords

Cadmium, Melatonin, Toxicity, Pregnancy

References

• Akyolcu, M.C., Ozcelik, D., Durseu, S., Toplan, S., Kahraman, R. (2003). Accumulation of cadmium in tissue ve its effect on live performance. J Phys IV France, 107, 333–336
• Alharbi, N., Elobeid, M., Virk, P. (2019). Protective effect of quercetin treatment against cadmium-induced oxidative stress in a male rat model. Pakistan J Zool 15,(6), 2287-96. DOI: http://dx.doi.org/10.17582/journal.pjz/(2019).51.6.2287.2296
• Arroyo, S., Flores, M., Ortiz, B., Gómez-Quiroz, E., Gutiérrez-Ruiz, C. (2012). Liver ve cadmium toxicity. J Drug Metab Toxicol S, 5,1-9.
• Aydoğdu, N., Kanter, M., Erbaş, H., Kaymak, K. (2007). Kadmiyuma bağli karaciğer hasarinda taurin, melatonin ve asetilsisteinin nitrik oksit, lipid peroksidasyonu ve bazi antioksidanlar üzerindeki etkileri. Erciyes Tıp Fak Derg, 29,(2), 89-96.
• Beyrami, M., Karimi, E., Oskoueian, E. (2020). Synthesized chrysin-loaded nanoliposomes improves cadmium-induced toxicity in mice. Environ Sci Pollut Res, 27, 40643–40651 https://doi.org/10.1007/s11356-020-10113-7
• Cvean, D., Bayram Ş, Calapoğlu N, Gürbüz N, Cankara M (2017). Effect of melatonin ve selenium on reproductive system of cadmium given Female Rats. SDU Med Fac, J 24 (3) 84-95, 10.17343/sdutfd.270310
• Cao, H., Gao, F., Xia, B., Zhang, M., Liao, Y., Yang, Z., Zhang, C. (2016). Alterations in trace element levels ve mRNA expression of Hsps ve inflammatory cytokines in livers of duck exposed to molybdenum or/ve cadmium. Ecotoxicology ve Environmental Safety, 125, 93-101.https://doi.org/10.1016/j.ecoenv.(2015).12.003
• Carlomagno, G., Minini, M., Tilotta, M., Unfer, V. (2018). From implantation to birth: insight into molecular melatonin functions. International Journal of Molecular Sciences, 19 (9), 2802:https://doi.org/10.3390/ijms19092802
• Chen, Q., Zhang, R., Nġu, Y., (2013). The protective effect of grape seed procyanidin extract against cadmium induced renal oxidative damage in mice. Environmental Toxicology ve Pharmacology, 36, 759–68
• Chen, Y., Zhou, C., Bian, Y., Fu. F., Zhao, X., Zhang, M., Ruan, H. (2023). Cadmium exposure promotes thyroid pyroptosis ve endocrine dysfunction by inhibiting Nrf2/Keap1 signaling. Ecotoxicology ve Environmental Safety 249, 114376.
• Chmur, M., & Bajguz, A. (2023). Melatonin involved in protective effects against cadmium stress in Wolffia Arrhiza. International Journal of Molecular Sciences, 24 (2), 1178.
• Chwełatiuk, E., Włostowki, T., Krasowska, A., Bonda, E. (2006). The effect of orally administered melatonin on tissue accumulation ve toxicity of cadmium in mice. Journal of Trace Elements in Medicine ve Biology, 19 (4), 259-65.
• Deveci, A., Gökhan, R., Kükürt, A., Mushap, K., & Deveci, A. (2023). The protective effect of caffeic acid phenethyl 5 ester on cadmium-induced liver toxicity: A histopathological ve biochemical study. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 1-23.
• El-Demerdash, F.M., Yousef, M.I., Kedwany, F.S., Baghdadi, H.H. (2004). Cadmium induced changes in lipid peroxidation, blood hematology, biochemical parameters ve semen quality of male rats: protective role of vitamin E ve ß-carotene. Food Chem Toxicol, 42, 1563-71.
• El-Neweshy, S., Srag, A. (2011). Chronic malachite green toxicity in nile tilapia: pathological ve haematological studies with special reference to quantitative histopathological assessment. Researcher 3 (4), 55-64.
• El-Sokkary, G., Nafady, A., Shabash, H. (2010). Melatonin administration ameliorates cadmium-induced oxidative stress ve morphological changes in the liver of rat. Ecotoxicol Environ Saf, 73, 456-63. https://doi.org/10.1016/j.ecoenv.2009.09.014
• Erdem, T., Hatipoğlu, F. (2011). Pathology of single dose cadmium toxicity ve investigations of protective effect of simultaneous chlorpromazine administrations in rats. Eurasian Journal of Veterinary Sciences 27 (1), 45-58.
• Farhan, S. (2020). Effects of tribulus terrestris fruits on renal ve lung tissues in female mice administered with cadmium. World's Veterinary Journal, 10 (3), 414-0. DOI: https://dx.doi.org/10.36380/scil.(2020).wvj51.
• Feng, X., Jin, R., Zhou, Q., Jiang, Y., Wang, X., Zhang, J. (2022). Deep learning approach identified a gene signature predictive of the severity of renal damage caused by chronic cadmium accumulation. J Hazard Mater,433 Article 128795, 10.1016/j.jhazmat.(2022).128795
• Fouad A, Jresat I. (2015). Thymoquinone therapy abrogates toxic effect of cadmium on rat testes. Verologia 47, 417–26, https://doi.org/10.1111/ve.12281
• Güneş, E., & Şensoy, E. (2020). The effect of Turkısh coffee ve cadmıum acetate on Drosophila Melanogaster. Journal of International Environmental Application ve Science, 15 (1), 1-8.
• Güneş, E., & Şensoy, E. (2022). Is Turkish coffee protects Drosophila melanogaster on cadmium acetate toxicity by promoting antioxidant enzymes?. Chemosphere, 296, 133972.
• Gökalp, O., Mehmet, Ö., Ahmet, K., Çiçek, E., Sütçü, R., Koçak, A., Aktürk, O. (2005), Ratlarda kadmiyumun pankreasa etkileri. SDÜ Tıp Fakültesi Dergisi 12 (3), 27-30.
• Hagar, H., Al Malki, W. (2014). Betaine supplementation protects against renal injury induced by cadmium intoxication in rats: role of oxidative stress ve caspase-3. Environmental Toxicology ve Pharmacology 37 (2), 803-11.
• Hyun, M., Kim, H., Kim, J., Lee, J., Lee, J., Rathor, L., & Heo, D. (2023). Melatonin protects against cadmium-induced oxidative stress via mitochondrial STAT3 signaling in human prostate stromal cells. Communications Biology, 6 (1), 157.
• Howard, A., Kuznietsova, H., Dziubenko, N., Aigle, A., Natuzzi, M., Thomas, E., Tillement, O. (2023). Combating lead ve cadmium exposure with an orally administered chitosan-based chelating polymer. Scientific Reports, 13(1), 2215. https://doi.org/10.1038/s41598-023-28968-4.
• Janicka, M., Binkowski, Ł.J., Błaszczyk, M., Paluch, J., Wojtaś, W. (2015). Cadmium, lead ve mercury concentrations ve their influence on morphological parameters in blood donors from different age groups from southern Polve. Journal of Trace Elements in Medicine ve Biology , 29, 342-6.
• Jiang, Z., Xu, D., Yao, X., Liu, W., Liu, N., Wang, Q. (2022). An integrated multi-omics approach revealed the regulation of melatonin on age-dependent mitochondrial function impair ve lipid dyshomeostasis in mice hippocampus. Pharmacol Res,179,1 Article 106210, 10.1016/j.phrs.(2022).106210
• Kaplan, M., Atakan, H., Aydoğdu, N., Aktoz, T., Puyan, Ö., Şeren, G., Tokuç, B., İnci, O. (2009). The effect of melatonin on cadmium-induced renal injury in chronically exposed rats. Turkish Journal of Urology, 35 (2), 139-147
• Karaca, Ö., Sunay, B., Kuş, A., Gülcen, B., Özcan, E., Ögetürk, M., Kuş, İ. (2014). Investigation of the effects of melatonin against cadmium-induced experimental liver injury at biochemical ve histopathological levels. Firat Medical Journal, 19 (3), 110-5. info:eu-repo/semantics/openAccess
• Kumar, N., Kumari, V., Ram, C., Kumar, B.S.B., Verma, S. (2018). Impact of oral cadmium intoxication on levels of different essential trace elements ve oxidative stress measures in mice: a response to dose. Environ Sci Pollut Res, 25, 5401–1.https://doi.org/10.1007/s11356-017-0868-3.
• Küçük, S., Midilli, S., Güler, M., Çoban, D. (2018). Kadmiyuma maruz bırakılmış Sarı Prenses (Labidochromis caeruleus) balıklarında saptanan histolojik değişiklikler üzerine bir ön çalışma. Ege Journal of Fisheries ve Aquatic Sciences, 35(3), 261-266.
• Liu, J., Pang, J., Tu, C., Wang, H., Sha, M., Shao, H., Liu, X. (2019). The accumulation, histopathology, ve intestinal microorganism effects of waterborne cadmium on Carassius auratus gibelio. Fish Physiology Ve Biochemistry, 45,231-243.https://doi.org/10.1007/s10695-018-0557-2
• Liu, W., Liu, Y., Lu, H., Tian, C., Duan. L. (2018). Piperlongumine restores the balance of autophagy ve apoptosis by increasing BCL2 phosphorylation in rotenone-induced Parkinson disease models. Autophagy, 14 (5), 845-61.https://doi.org/10.1515/reveh-(2019)-0016
• Mohammadi, P., Rahimifard, M., Baeeri, M., Abdollahi, M., Mostafalou, S. (2019). Mechanistic assessment of cadmium toxicity in association with the functions of estrogen receptors in the Langerhans islets. Iranian Journal of Basic Medical Sciences, 22 (4),445.doı:10.22038/IJBMS.(2019).33939.8076.
• Omer, A., Elobeid, A., Fouad, D., Daghestani, H., Al-Olayan, E. (2012). Cadmium bioaccumulation ve toxicity in tilapia fish (Oreochromis niloticus). Journal of Animal ve Veterinary Advance, 11 (10), 1601-6.
• Pivonello, C., Negri, M., Patalano, R., Amatrudo, F., Montò, T., Liccardi, A., Colao. K, (2022). The role of melatonin in the molecular mechanisms underlying metaflammation ve infections in obesity: A narrative review. Obesity Reviews,23 (3), e13390.https://doi.org/10.1111/obr.13390
• Rahbarghazi, R., Farhoudi, M., Rahmani-Youshanlouei, H., Hassanpour, M., Rahbarghazi, A., Rezaie, J., Ahmadi, M. (2022). Putative effect of melatonin on cardiomyocyte senescence in mice with type 1 diabetes mellitus. Journal of Diabetes ve Metabolic Disorders, 21 (1), 353-9. 10.1007/s40200-022-00982-9
• Renugadevi, J., Milton, P.S. (2010). Cadmium induced hepatotoxicity in rats ve the protective effect of naringin. Exp Toxicol Pathol, 62, 171–1.
• Saedi, S., Jafarzadeh, T., Shirazi, R., Totonchi, M. (2020). Effect of prepubertal exposure to CdCl2 on the liver, hematological, ve biochemical parameters in female rats: an experimental study. Biological Trace Element Research,194,472–81. https://doi.org/10.1007/s1(2011)-019-01800-194, 472-481
• Satarug, S., Vesey, A., Gobe, C. (2017). Health risk assessment of dietary cadmium intake: do current guidelines indicate how much is safe? Environmental Health Perspectives125 (3), 284-8.
• Shen, Y., Jiang, Z., Zhong, X., Wang, H., Liu, Y., Li, X. (2022). Manipulation of cadmium ve diethylhexyl phthalate on Rana chensinensis tadpoles affects the intestinal microbiota ve fatty acid metabolism. Science of The Total Environment, 821,153455.https://doi.org/10.1016/j.scitotenv.(2022).153455
• Sigma-Aldrich,https://www.sigmaaldrich.com/TR/en/sds/ALDRICH/202908 Erişim tarihi: 15.03. (2023)
• Şensoy, E. (2023). Investigation of the effect of Cadmium chloride applied during pregnancy on the morphological parameters of mouse offspring ve the protective role of melatonin. Journal of Hazardous Materials Advances, 9,100222.https://doi.org/10.1016/j.hazadv.(2022).100222
• Şensoy, E., Öznurlu, Y. (2019). Determination of the changes on the small intestine of pregnant mice by histological, enzyme histochemical, ve immunohistochemical methods. The Turkish Journal of Gastroenterology, 30(10), 917. doi: 10.5152/tjg.(2019).18681
• Wilkinson, D., Shepherd, E., Wallace, M. (2016). Melatonin for women in pregnancy for neuroprotection of the fetus. Cochrane Database of Systematic Reviews, 1 (3), 1-8, https://doi.org/10.1002/14651858.CD010527.pub2
• Xia, B., Cao, H., Luo, J. (2015). The Co-induced effects of molybdenum ve cadmium on antioxidants ve heat shock proteins in duck kidneys. Biol Trace Elem Res 168, 261–268 https://doi.org/10.1007/s1(2011)-015-0348-x
• Xiong, W., Xu, F., Zhu, L., Cao, L., Yi, J., Shi, T., Wang, H. (2021). Environmental exposure to cadmium impairs fetal growth ve placental angiogenesis via GCN-2-mediated mitochondrial stress. Journal of Hazardous Material,401 (5), 1-10, 123438. https://doi.org/10.1016/j.jhazmat.(2020).123438
• Yu, Y., Liew, Z., Wang, A., Arah, A., Li. J., Olsen, J., Li, J. (2019). Mediating roles of preterm birth ve restricted fetal growth in the relationship between maternal education ve infant mortality: A Danish population-based cohort study. PLoS Medicine, 16 (6), e1002831. https://doi.org/10.1371/journal.pmed.1002831
• Zargar, S., Siddiqi, J., Al Daihan, K., Wani, A. (2015). Protective effects of quercetin on cadmium fluoride induced oxidative stress at different intervals of time in mouse liver. Acta Biochimica Polonica, 62 (2), 1-10.
• Zhang, H., Liu, X., Zheng, Y., Zha, X., Elsabagh, M., Zhang, Y., Wang, H. (2022). Effects of the maternal gut microbiome ve gut-placental axis on melatonin efficacy in alleviating cadmium-induced fetal growth restriction. Ecotoxicology ve Environmental Safety , 237, 113550.https://doi.org/10.1016/j.ecoenv.(2022).113550
• Zhang, W., Yan, J., Wang, J. (2007). Comparative studies on the increae of uterine weight ve related mechanisms of cadmium ve pnonylphenol. Toxicology 241, 84–91
• Zhou, X., Liu, B., Dai, M., Zhu, L., Xiong, W., Li, X., Wang, H. (2022). Environmental cadmium impairs blood-testis barrier via activating HRI-responsive mitochondrial stress in mice. Science of The Total Environment 810, 152247. 10.1016/j.scitotenv.(2021).152247
• Zhu, L., Dai, M., Xiong, W., Shi, T., Liu, B., Fu, T., Wang, H. (2022). Gestational exposure to environmental cadmium induces placental apoptosis ve fetal growth restriction via Parkin-modulated MCL-1 degradation. Journal of Hazardous Materials, 424 (A), 1-15, 127268.https://doi.org/10.1016/j.jhazmat.(2021).127268
• Zhu, L., Xu, F., Shi, T., Feng, J., Xiong, W., Nan, Y., Zhang, C. (2019). Activation of autophagy inhibits cadmium-triggered apoptosis in human placental trophoblasts ve mouse placenta. EnvironPollut,254 (A), Article, 1,10.https://doi.org/10.1016/j.envpol.(2019).112991.